We have previously reported that retinal pigment epithelial (RPE) cells make a number of growth factors such as the insulin-like growth factor-1 (IGF-1). In fact, several systems have been found to be present that could self-regulate growth and metabolic activity in the retinal pigment epithelium and be involved in eye diseases. These specific growth and differentiating factors can guide development and interactions of individual ocular tissues to form a functional visual system. This particular project is focused on an understanding of the growth and neurotrophic factors that control normal and abnormal photoreceptor development. In this regard, we have cloned and characterized a unique differentiating protein secreted from fetal human pigment epithelial cells, called pigment epithelial-derived factor, that is neurotropic to cultured human retinoblastoma cells and may affect neural retinal development in vivo. This protein also is a potent neuron survival protein in that it promotes neuronal cell survival of cultured brain cells. Finally, it is a candidate gene in retinal degenerations because it maps to the p13.3 location on chromosome 17, an area in which a gene for retinitis pigmentosa has been mapped.